chr8-127448159-A-G

Variant names:

• chr8-127448159-A-G
• rs6470517
• ENST00000502056.1:n.1042-4439T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502056.1(CASC8):​n.1042-4439T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,240 control chromosomes in the GnomAD database, including 1,875 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1875 hom., cov: 32)
• Consequence: CASC8 ENST00000502056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 9 publications found

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502056.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_024393.1		n.1042-4439T>C		intron	N/A
	CASC8	NR_117100.1		n.1042-27196T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000502056.1	TSL:1	n.1042-4439T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1042-27196T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22854 AN: 152122 Hom.: 1871 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0936

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22873 AN: 152240 Hom.: 1875 Cov.: 32 AF XY: 0.148 AC XY: 10991 AN XY: 74430

African (AFR) AF: 0.177 AC: 7356 AN: 41542

American (AMR) AF: 0.107 AC: 1632 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3470

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5184

South Asian (SAS) AF: 0.0939 AC: 453 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10604

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10243 AN: 68014

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.151 Hom.: 1853

Bravo AF: 0.147

Asia WGS AF: 0.0590 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6470517;

hg19: chr8-128460404;